主动脉瓣钙化是各种心脏疾病的危险因素之一，但其发病机制未清。现发现：主动脉瓣膜钙化病人中FSTL1分泌降低，与年龄呈负相关性，而钙化瓣膜中瓣膜间质细胞表达量显著下降。FSTL1可抑制瓣膜间质细胞钙化程度，而其表达受Sirt1/4调控。其作用受体为DIP2A及CD14，芯片提示FSTL1调控SOX9等基因。这提示了FSTL1通过多重调控作用对抗瓣膜间质细胞钙化过程是主动脉瓣膜钙化进展的重要机制。因此，本研究将探讨：1）钙化对Sirt1/4表达调控模式；2）Sirt1/4调控FSTL1表达的机制；3）STL1受体对主动脉瓣膜钙化的作用及相互间关系； 4）FSTL1对SOX9-RUNX2轴的调控机制； 5）在体研究FSTL1对主动脉瓣膜钙化进展的调控机制。通过以上研究以期阐释FSTL1对主动脉瓣膜钙化发展的相关机制，为在体干预治疗主动脉瓣膜钙化提供科学依据及实验基础。

Calcific aortic valve is one of a variety of risk factors for heart disease, but the pathogenesis is not clear. Now we found that: the expression of FSTL1 is decreased in serum and valve interstitial cells of valve tissues of aortic valve calcification, and negative related with age. Sirt1 and Sirt4 regulated the expression of FSTL1 in valve interstitial cells. Moreover, FSTL1 inhibited the calcification of valve interstitial cells and bind with DIP2A and CD14 as its receptor. The gene chip array showed that FSTL1 regulated SOX9 and RUNX2. These results hint that FSTL1 regulated valvular interstitial cells calcification process via multiple signaling pathways, which is an important mechanism of aortic valve calcification progression. Therefore, this study will examine: 1) calcification process regulated Sirt1/4 expression; 2) the expression of FSTL1 is regulated via Sirt1/4; 3) receptors of FSTL1 effect on aortic valve calcification; 4) the mechanism of SOX9-RUNX2 axis was regulated via FSTL1; 5) in vivo, the aortic valve calcification progress of FSTL1 regulatory mechanisms. Through these studies to explain the mechanisms of aortic valve calcification regulated by FSTL1, which provide a scientific basis and experimental basis for therapeutic intervention in vivo aortic valve calcification.